Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1982 Nov;14(5):677–682. doi: 10.1111/j.1365-2125.1982.tb04956.x

RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability.

A Darragh, R Lambe, M Kenny, I Brick, W Taaffe, C O'Boyle
PMCID: PMC1427482  PMID: 6814472

Abstract

1 In a double-blind, placebo controlled study, the efficacy of Ro 15-1788, a new benzodiazepine antagonist, in blocking the cognitive, psychomotor and subjective effects of diazepam, was investigated in a group of six healthy male volunteers. 2 The central effects of orally administered diazepam (40 mg) were most pronounced 1 h after dosing and persisted for 9 h with decreasing severity. 3 Concurrent oral administration of Ro 15-1788 (200 mg) completely prevented the impairment in cognitive and psychomotor function observed after diazepam alone. 4 The duration of action of Ro 15-1788 was shorter than that of diazepam. 5 Plasma diazepam levels after administration of the diazepam/antagonist combination were very similar to those observed following diazepam alone.

Full text

PDF
677

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell E. F. The use of naloxone in the treatment of diazepam poisoning. J Pediatr. 1975 Nov;87(5):803–804. doi: 10.1016/s0022-3476(75)80315-5. [DOI] [PubMed] [Google Scholar]
  2. Bell E. F. The use of naloxone in the treatment of diazepam poisoning. J Pediatr. 1975 Nov;87(5):803–804. doi: 10.1016/s0022-3476(75)80315-5. [DOI] [PubMed] [Google Scholar]
  3. Bond A. J., Lader M. H. The residual effects of flurazepam. Psychopharmacologia. 1973 Sep 28;32(3):223–235. doi: 10.1007/BF00422145. [DOI] [PubMed] [Google Scholar]
  4. Christensen K. N., Hüttel M. Naloxone does not antagonize diazepam-induced sedation. Anesthesiology. 1979 Aug;51(2):187–187. doi: 10.1097/00000542-197908000-00035. [DOI] [PubMed] [Google Scholar]
  5. Costa E., Guidotti A., Toffano G. Molecular mechanisms mediating the action of diazepam on GABA receptors. Br J Psychiatry. 1978 Sep;133:239–248. doi: 10.1192/bjp.133.3.239. [DOI] [PubMed] [Google Scholar]
  6. Darragh A., Lambe R., Brick I., Downie W. W. Reversal of benzodiazepine-induced sedation by intravenous Ro 15-1788. Lancet. 1981 Nov 7;2(8254):1042–1042. doi: 10.1016/s0140-6736(81)91233-2. [DOI] [PubMed] [Google Scholar]
  7. Darragh A., Lambe R., Scully M., Brick I., O'Boyle C., Downe W. W. Investigation in man of the efficacy of a benzodiazepine antagonist, Ro 15-1788. Lancet. 1981 Jul 4;2(8236):8–10. doi: 10.1016/s0140-6736(81)90251-8. [DOI] [PubMed] [Google Scholar]
  8. Hunkeler W., Möhler H., Pieri L., Polc P., Bonetti E. P., Cumin R., Schaffner R., Haefely W. Selective antagonists of benzodiazepines. Nature. 1981 Apr 9;290(5806):514–516. doi: 10.1038/290514a0. [DOI] [PubMed] [Google Scholar]
  9. Kleinknecht R. A., Donaldson D. A review of the effects of diazepam on cognitive and psychomotor performance. J Nerv Ment Dis. 1975 Dec;161(6):399–414. doi: 10.1097/00005053-197512000-00004. [DOI] [PubMed] [Google Scholar]
  10. McNair D. M. Antianxiety drugs and human performance. Arch Gen Psychiatry. 1973 Nov;29(5):611–617. doi: 10.1001/archpsyc.1973.04200050024004. [DOI] [PubMed] [Google Scholar]
  11. Möhler H., Okada T. Benzodiazepine receptor: demonstration in the central nervous system. Science. 1977 Nov 25;198(4319):849–851. doi: 10.1126/science.918669. [DOI] [PubMed] [Google Scholar]
  12. Möhler H., Okada T. Properties of 3H-diazepam binding to benzodiazepine receptors in rat cerebral cortex. Life Sci. 1977 Jun 15;20(12):2101–2110. doi: 10.1016/0024-3205(77)90191-6. [DOI] [PubMed] [Google Scholar]
  13. Möhler H., Okada T. The benzodiazepine receptor in normal and pathological human brain. Br J Psychiatry. 1978 Sep;133:261–268. doi: 10.1192/bjp.133.3.261. [DOI] [PubMed] [Google Scholar]
  14. Polc P., Laurent J. P., Scherschlicht R., Haefely W. Electrophysiological studies on the specific benzodiazepine antagonist Ro 15-1788. Naunyn Schmiedebergs Arch Pharmacol. 1981 Jul;316(4):317–325. doi: 10.1007/BF00501364. [DOI] [PubMed] [Google Scholar]
  15. Rupreht J. Physostigmine reversal of diazepam. Anesthesiology. 1980 Aug;53(2):180–181. doi: 10.1097/00000542-198008000-00020. [DOI] [PubMed] [Google Scholar]
  16. Sedman A. J., Wagner J. G. CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci. 1976 Jul;65(7):1006–1010. doi: 10.1002/jps.2600650713. [DOI] [PubMed] [Google Scholar]
  17. Squires R. F., Brastrup C. Benzodiazepine receptors in rat brain. Nature. 1977 Apr 21;266(5604):732–734. doi: 10.1038/266732a0. [DOI] [PubMed] [Google Scholar]
  18. Tallman J. F., Paul S. M., Skolnick P., Gallager D. W. Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science. 1980 Jan 18;207(4428):274–281. doi: 10.1126/science.6101294. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES